Implantable Electrode Positioning

ABSTRACT

A method of surgically positioning an electrode array at a desired implantation location relative to a nerve. A temporary probe electrode is temporarily positioned adjacent to the nerve and at a location which is caudorostrally separate to the desired implantation location of the electrode array. The implanted position of the probe electrode is temporarily fixed relative to the nerve. During implantation of the electrode array, electrical stimuli are applied from one of the temporarily fixed probe electrode and the electrode array, to evoke compound action potentials on the nerve. Compound action potentials evoked by the stimuli are sensed from at least one electrode of the other of the temporarily fixed probe electrode and the electrode array. From the sensed compound action potentials a position of the electrode array relative to the nerve is determined.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of Australian Provisional PatentApplication No. 2014905030 filed 11 Dec. 2014, which is incorporatedherein by reference

TECHNICAL FIELD

The present invention relates to monitoring compound action potentialsduring surgery to assist with implantable electrode placement.

BACKGROUND OF THE INVENTION

A range of implanted neural devices exist, including: spinal cordimplants which electrically stimulate the spinal column in order tosuppress chronic pain; cochlear implants which electrically stimulatethe auditory nerve to produce a hearing sensation; deep brainstimulators which electrically stimulate selected regions of the brainto treat conditions such as Parkinson's disease or epilepsy; and neuralbypass devices which electrically stimulate either afferent sensorynerve fibres to reproduce impaired sensory function or efferent motornerve fibres to reproduce impaired motor activity, or both.

Such devices require implantation of an electrode array proximal to theneural pathway of interest, in order to enable electrical stimuli to bedelivered from the array to the nerve in order to evoke compound actionpotentials, or neural responses. For example, the typical procedure forimplantation of a spinal cord stimulator having a paddle electrodeinvolves placing the patient under general anaesthesia and performing alaminectomy or removal of part of the dorsal process to access theepidural space. However the success of spinal cord stimulation for painrelief, and of neural device implantation in general, is strongly linkedto the accuracy of the placement of the implanted stimulating electrodesduring surgery. Physiologic midline placement of paddle leads isimportant to avoid uncomfortable side-effects during stimulation as aresult of the activation of dorsal root fibers. One approach toaccurately position the electrode array is to temporarily wake thepatient from the general anaesthesia and to ask the patient to reportthe location of paraesthesia produced by stimuli delivered by the array.Temporarily waking a patient from a general can be difficult, and evenonce the patient is awake the reports provided by a drowsy patient areoften unreliable. Because the patient is not fully alert whentemporarily awoken from general anaesthesia, and is otherwise asleepduring the remainder of the implantation procedure, they can onlyprovide limited feedback regarding the location of the paraesthesia, orregarding any complications arising from lead placement. Althoughcomplications are rare they can be very serious.

Another option is to not wake the patient during surgery, and to useanatomical targeting to guide the positioning of the electrode array, byreference to anatomical markers that can be imaged via fluoroscopy,instead of relying on unreliable patient feedback. However, fluoroscopicimaging resolution is relatively imprecise, compared to the accuracyrequirements of lead placement. Moreover, complications of implanting asurgical lead while a patient is asleep can include damage to the spinalcord due to direct pressure of the lead as it is placed into theepidural space, or post-operative damage due to the development of ahematoma over the lead, which can then create pressure on the lead anddamage the dorsal column axons.

Another situation requiring accurate electrode lead placement is thecase of paddle leads, which comprise a two dimensional array ofelectrodes which when implanted into the epidural space extend bothalong (caudorostrally relative to) and across (mediolaterally relativeto) the dorsal columns. Paddle leads for example can be used to treatpatients with bilateral pain complaints, with the goal to provideparaesthesia to both sides of the body. To accomplish this it ispreferable to place the paddle lead over the physiologic midline of thedorsal columns. However the physiologic midline, being the centre lineof the spinal cord which demarcates between the fibres innervating theleft side and the right side of the body, may or may not be well alignedwith the anatomical midline as defined by anatomical markers that can beimaged via fluoroscopy. Consequently, implanting a patient under ageneral anaesthetic by reference to anatomical markers can result in thepaddle electrode array not providing equal stimulation and paraesthesiato both sides of the body.

One technique for defining the physiologic midline is to usesomatosensory potentials, observed from electrodes placed on the scalp.In this technique the stimulation of peripheral nerve fibres, such asstimulation of the posterior tibial nerve by needle electrode, evokes aresponse in the somatosensory cortex. By simultaneously stimulatingdorsal column fibres using the spinal cord lead, a collision can becreated between the peripherally evoked response and the spinally evokedresponse. This collision results in an observed depression of thesomatosensory responses. Both tibial nerves are stimulated, so that asymmetric depression from left and right somatosensory cortex responseswill indicate that the stimulated electrode is above the midline.

Somatosensory response to stimulation of peripheral nerves has also beenused to identify the rostral caudal location of the electrode withrespect to peripheral locations. However, this has been less successfulas when considering a sensory homunculus the representation of the legsfor example on the sensory cortex is small, and buried within thelongitudinal fissure of the brain. Since many chronic pain patients havelower extremity pain this method has not proved to be useful. Anothermethod has been to record motor evoked potentials from the muscles inthe periphery in response to stimulation at the spinal cord. Althoughmore successful at activating muscle fibres, dorsal column motorstimulation requires very high currents and as such does not closelycorrespond to the area of sensory activation.

The dorsoventral position of the electrode array is also of importance,as a large nerve-to-electrode distance can increase the stimulus powerrequired to evoke neural responses and thus decrease battery life. Alarge electrode-to-nerve distance can also decrease the strength ofobserved neural signals reaching sense electrodes, in devices configuredto measure the neural responses. On the other hand, bringing theelectrode array too close to the nerve can apply pressure or directtrauma to the nerve and cause temporary or even permanent nerve damage.However, the dorsoventral position is also difficult to accuratelydetermine during surgery. Occasionally a surgeon may take a lateral viewimage with fluoroscope, however these images are not of sufficientresolution to sufficiently accurately judge the proximity of the arrayto the cord.

Any discussion of documents, acts, materials, devices, articles or thelike which has been included in the present specification is solely forthe purpose of providing a context for the present invention. It is notto be taken as an admission that any or all of these matters form partof the prior art base or were common general knowledge in the fieldrelevant to the present invention as it existed before the priority dateof each claim of this application.

Throughout this specification the word “comprise”, or variations such as“comprises” or “comprising”, will be understood to imply the inclusionof a stated element, integer or step, or group of elements, integers orsteps, but not the exclusion of any other element, integer or step, orgroup of elements, integers or steps.

In this specification, a statement that an element may be “at least oneof” a list of options is to be understood that the element may be anyone of the listed options, or may be any combination of two or more ofthe listed options.

SUMMARY OF THE INVENTION

According to a first aspect the present invention provides a method ofsurgically positioning an electrode array at a desired implantationlocation relative to a nerve, the method comprising:

-   -   implanting a temporary probe electrode adjacent to the nerve and        at a location which is caudorostrally separate to the desired        implantation location of the electrode array;    -   temporarily fixing the implanted position of the probe electrode        relative to the nerve;    -   during implantation of the electrode array, applying electrical        stimuli from one of the temporarily fixed probe electrode and        the electrode array, to evoke compound action potentials on the        nerve;    -   sensing, from at least one electrode of the other of the        temporarily fixed probe electrode and the electrode array, the        compound action potentials evoked by the stimuli; and    -   determining from the sensed compound action potentials a        position of the electrode array relative to the nerve.

According to a second aspect the present invention provides a system forpositioning an electrode array at a desired implantation locationrelative to a nerve, the system comprising:

-   -   a temporary probe electrode configured to be implanted adjacent        to the nerve at a location which is caudorostrally separate to        the desired implantation location of the electrode array, and        configured to be temporarily fixed relative to the nerve while        implanted;    -   an electrode array configured to be implanted adjacent to the        nerve at the desired implantation location, and comprising at        least one electrode configured to evoke or sense compound action        potentials; and    -   a controller configured to:        -   cause electrical stimuli to be applied from one of the            temporarily fixed probe electrode and the electrode array to            evoke compound action potentials on the nerve during            implantation of the electrode array;        -   sense from at least one electrode of the other of the            temporarily fixed probe electrode and the electrode array            the compound action potentials evoked by the stimuli; and        -   determine from the sensed compound action potentials a            position of the electrode array relative to the nerve.

A non-transitory computer readable medium for surgically positioning anelectrode array at a desired implantation location relative to a nerve,comprising instructions which, when executed by one or more processors,causes performance of the following:

-   -   computer program code means for, during implantation of the        electrode array, applying electrical stimuli from one of the        electrode array and a probe electrode which is temporarily fixed        adjacent to the nerve at a location which is caudorostrally        separate to the desired implantation location of the electrode        array, to evoke compound action potentials on the nerve;    -   computer program code means for sensing, from at least one        electrode of the other of the electrode array and the probe        electrode, the compound action potentials evoked by the stimuli;        and    -   computer program code means for determining from the sensed        compound action potentials a position of the electrode array        relative to the nerve.

In some embodiments of the invention, the probe electrode is surgicallyintroduced via the same incision as the electrode array. In some suchembodiments the probe electrode may be fed from the incision in a firstcaudorostral direction which is opposite to a second caudorostraldirection in which the electrode array is introduced. In further suchembodiments, in which the nerve is the dorsal column, the probeelectrode may be temporarily fixed so as to be positioned in the same ora nearby vertebral segment as the electrode array. Temporarily fixingthe probe electrode near the electrode array, such as in the samevertebral segment or in an adjacent vertebral segment, or nearby withina small number of vertebral segments, is desirable because while thefibres of the dorsal column run approximately parallel over thedistances of a few vertebral segments, any twist or rotation of orwithin the spinal cord could produce a misalignment of theelectrophysiological midline relative to the anatomical midline and thisrisk rises beyond a few vertebral segments, and this might alter or makeunclear the spatial representation of the physiological midline of thenerve which is provided by the ECAPs when first evoked. Temporarilyfixing the probe electrode near the electrode array is also advantageouswhen it permits a single surgical incision to be used, such as a singlelaminectomy, to implant both the probe electrode and the electrodearray.

In some embodiments of the invention, the desired positioning of theelectrode array is relative mediolaterally to a physiologic midline ofthe nerve. For example, the desired mediolateral positioning of theelectrode array may be centrally over the midline of the nerve. In suchembodiments the probe electrode is preferably configured tosimultaneously stimulate an even distribution of fibres mediolaterallyacross the nerve. This may be achieved by the probe electrode comprisinga wide electrode element, or a plurality of electrode elements, whichextend(s) across substantially an entire mediolateral extent of thenerve, and/or by applying probe stimuli which are sufficiently large,such as being a multiple of 1.5, two or more of the threshold stimuluslevel, so as to evoke responses in most or all fibres of the nerve. Insuch embodiments the probe electrode thus launches a compound actionpotential along the fibres of the nerve which is substantiallyelectrically centred on the nerve, even though the probe electrodeitself will not necessarily be precisely centrally positioned.Identification of the physiologic midline of the nerve, and positioningof the electrode array relative to the identified midline, may then beachieved by providing two laterally spaced apart sense electrodes on theelectrode array, and monitoring a relative strength of the compoundaction potential sensed by each of the sense electrodes. If one senseelectrode senses a stronger compound action potential, that electrode islikely closer to the physiologic midline and the electrode array can bemediolaterally moved by the surgeon accordingly. If the sense electrodessense equally strong CAPs, they are likely equidistant mediolaterallyfrom, i.e. centrally positioned over, the physiologic midline of thenerve.

In additional or alternative embodiments of the invention a radialspacing of the electrode array from the nerve, such as a dorsoventralposition of a dorsal column stimulator, may be determined. In suchembodiments, the probe electrode preferably comprises first and secondstimulus electrodes each at distinct radii away from the nerve. Forexample where the probe electrode comprises a sheet substrate, first andsecond electrodes may be formed on opposing outer surfaces of the sheetand may thereby be positioned at radii from the nerve which differ bythe thickness of the sheet. The first and second probe electrodes maythen be used to deliver stimuli of equal intensity, at different times.A sense electrode of the electrode array being implanted is then used tosense a first intensity of the CAP evoked by the first probe electrode,and a second intensity of the CAP evoked by the second probe electrode.A difference between the first intensity and the second intensity maythen be used to estimate a radial spacing of the electrode array fromthe nerve. Notably, even though a height of the probe electrode abovethe nerve may not be known, such embodiments permit a relative height ofthe electrode array to be monitored by comparing the first and secondintensity measurements over time as the electrode array is moved duringimplantation.

The probe electrode may comprise multiple elements which arecaudorostrally spaced apart along the nerve, for example to facilitateembodiments in which the probe electrode senses ECAPs evoked by theelectrode array, and/or to enable an optimally caudorostrally positionedprobe electrode element to be selected in order to maximise recruitmentand or measurement sensitivity.

Because the ECAPs produced by the probe electrode are being used as apoint of reference during ongoing positioning of the electrode array,the probe electrode needs to be in a fixed location throughout theprocedure. The probe electrode may be fixed by being temporarilyanchored upon a vertebra, within the epidural space. Alternatively theprobe electrode may be fixed to an external structure such as a surgicalstabilising arm and have suitable longitudinal rigidity to maintain asubstantially constant implanted position relative to the nerve for theduration of the procedure, or may be fixed by any other suitabletemporary fixing means.

In some embodiments of the invention the probe electrode is a peripheralnerve stimulator delivering stimuli to evoke CAPs on peripheral nerve(s)at a location of interest such as a desired site of paraesthesia. Insome such embodiments, the electrode array which is being implanted maycomprise both stimulus electrodes and sense electrodes, whereby an arraylocation at which the sense electrodes sense a maximal collision of CAPsevoked by the stimulus electrodes with the CAPs evoked by the peripheralnerve stimulator is taken to be an optimal caudorostral position of thestimulus electrodes relative to the location of interest. Collision ofCAPs, being the reduced recruitment achieved by a given stimulus due tosome or all of the adjacent population of fibres being in theirrefractory period because of the peripherally evoked CAP, may bedetermined by a depression in the overall amplitude of sensed CAPs.Preferably the timing of the delivery of the dorsal column pulse isadjusted to uniquely detect collision.

The present invention thus recognises that sensing compound actionpotentials by use of electrodes of an electrode array, can be used tomonitor the placement of the electrode array during surgery. The presentinvention thus provides a method to better assess the position of theelectrode array, in the dorsoventral, caudorostral and/or mediolateraldirection, quickly and simply while the patient is under generalanaesthesia, without requiring scalp electrodes for somatosensory cortexmonitoring, for example.

It is to be appreciated that embodiments of the present invention may beimplemented in respect of any suitable neurostimulator such as spinalcord stimulators, cardiac pacemakers/defibrillators, functionalelectrical stimulators (FES), pain stimulators, etc.

The stimuli may be delivered by the probe electrode, and evoked ECAPsmay be sensed by the electrode array. Alternatively, the stimuli may bedelivered by the electrode array, and evoked ECAPs may be sensed by theprobe electrode, and it is to be understood that in all embodimentsdescribed herein the positioning roles of the probe electrode and theelectrode array may be reversed, within the scope of the presentinvention. Moreover, over time the source of stimuli may alternatebetween the probe electrode and the electrode array, which may assistwith position resolution.

BRIEF DESCRIPTION OF THE DRAWINGS

An example of the invention will now be described with reference to theaccompanying drawings, in which:

FIG. 1 schematically illustrates an implanted spinal cord stimulator;

FIG. 2 is a block diagram of the implanted neurostimulator;

FIG. 3 is a schematic illustrating interaction of the implantedstimulator with a nerve;

FIG. 4 is a view of the spinal cord through a conventional laminectomy;

FIG. 5a illustrates a probe electrode, and an electrode array beingpositioned, FIG. 5b illustrates the probe electrode evoking a neuralresponse, FIG. 5c illustrates measurement of the evoked response tolocate the physiologic midline of the nerve, in accordance with a firstembodiment of the invention, and FIGS. 5d and 5e illustrate experimentalverification of the principles of FIGS. 5a -5 c;

FIG. 6a illustrates electrode array positioning and channel allocationsin accordance with another embodiment of the invention, and FIG. 6bshows ECAP signals recorded from the arrangement of FIG. 6 a;

FIGS. 7a and 7b show recordings obtained from electrodes 13-16 duringthe implantation procedure;

FIGS. 8a and 8b show recordings obtained from electrodes 13-16 duringclosing,

FIG. 9a illustrates electrode array positioning and channel allocationsin accordance with another embodiment of the invention, and FIGS. 9b and9c illustrate ECAP signals obtained, during the procedure, at 3.39 mA ofstimulation;

FIG. 10a is a plot of ECAP signal strength obtained on Channel 16,during the procedure, as the stimulus current was increased from zero to2.2 mA, and FIG. 10b is a plot of ECAP signal strength obtained onChannel 16, during closing, as the stimulus current was increased fromzero to 2.2 mA;

FIG. 11 is a post operative CT image illustrating the lateral locationof the lead causing the late responses;

FIG. 12A illustrates variation of the amplitude of the observed ECAPresponse with the distance of the axon from the recording electrode,FIG. 12b illustrates an embodiment for assessing dorsoventral electrodeposition, and FIG. 12c illustrates observed ECAPs at differing electrodeheights;

FIG. 13 illustrates a probe electrode arrangement for assessingelectrode array height; and

FIGS. 14a and 14b illustrate another embodiment of the invention inwhich ECAPs evoked directly on the spinal cord are combined withperipheral nerve stimulation.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 schematically illustrates an implanted spinal cord stimulator100. Stimulator 100 comprises an electronics module 110 implanted at asuitable location in the patient's abdomen and an electrode assembly 150implanted within the epidural space and connected to the module 110 by asuitable lead.

FIG. 2 is a block diagram of the implanted neurostimulator 100. Module110 contains a battery 112 and a telemetry module 114. In embodiments ofthe present invention, any suitable type of transcutaneouscommunication, such as infrared (IR), electromagnetic, capacitive andinductive transfer, may be used by telemetry module 114 to transferpower and/or data between an external device and the electronics module110.

Module controller 116 has an associated memory 118 storing patientsettings 120, control programs 122 and the like. Controller 116 controlsa pulse generator 124 to generate stimuli in the form of current pulsesin accordance with the patient settings 120 and control programs 122.Electrode selection module 126 switches the generated pulses to theappropriate electrode(s) of electrode array 150, for delivery of thecurrent pulse to the tissue surrounding the selected electrode.Measurement circuitry 128 is configured to capture measurements ofneural responses sensed at sense electrode(s) of the electrode array asselected by electrode selection module 126.

FIG. 3 is a schematic illustrating interaction of the implantedstimulator 100 with a nerve 180, in this case the spinal cord. Electrodeselection module 126 selects a stimulation electrode 2 of electrodearray 150 to deliver a current pulse to surrounding tissue includingnerve 180, and also selects a return electrode 4 of the array 150 forcurrent recovery to maintain a zero net charge transfer.

Delivery of an appropriate stimulus to the nerve 180 evokes a neuralresponse comprising a compound action potential which will propagatealong the nerve 180 as illustrated, for therapeutic purposes which inthe case of spinal cord stimulator for chronic pain is to createparaesthesia at a desired location.

The device 100 is further configured to sense the existence andintensity of compound action potentials (CAPs) propagating along nerve180, whether such CAPs are evoked by the stimulus from electrodes 2 and4, or otherwise evoked. To this end, any electrodes of the array 150 maybe selected by the electrode selection module 126 to serve asmeasurement electrode 6 and measurement reference electrode 8. Signalssensed by the measurement electrodes 6 and 8 are passed to measurementcircuitry 128, which for example may operate in accordance with theteachings of International Patent Application Publication No.WO2012155183 by the present applicant, the content of which isincorporated herein by reference.

FIG. 4 is a view of the spinal cord through a conventional laminectomy.Some embodiments provide for insertion of a probe electrode through sucha surgical incision and in the caudal direction within the epiduralspace, and the simultaneous implantation of an electrode array throughthe same incision and then in the rostral direction within the epiduralspace.

Referring to FIG. 4, the lamina is a posterior arch of the vertebralbone lying between the spinous process (which juts out in the middle)and the more lateral pedicles and the transverse processes of eachvertebra. The pair of laminae, along with the spinous process, make upthe posterior wall of the bony spinal canal. A conventional laminectomyinvolves excision of the posterior spinal ligament and some or all ofthe spinous process. Removal of these structures with an open techniquerequires disconnecting the many muscles of the back attached to them.After the laminectomy is performed the electrode is then positioned inplace with forceps or other tool by sliding the electrode in the rostraldirection into the epidural space. Conventionally, direct visual orradiographic examination is used to determine the position of theelectrode.

The arrangement shown in FIG. 5a separates the probe electrode from therecording electrode. The probe electrode can be arranged on a surgicaltool, which can be positioned over the dorsal column and, importantly,kept stationary while the recording electrode is moved. The probeelectrode may be placed caudally or rostrally of the electrode array.The probe electrode(s) are designed to stimulate a large area of thecord and are temporarily placed at the time of surgery.

FIGS. 5a-5c illustrate such an arrangement. In FIG. 5a the electrodearray 150 is inserted rostrally, while probe electrode 500 is insertedcaudally. The probe electrode 500 is preferably attached to a handle onsurgical tool to allow for simple placement. The insertion tool(s) usedallow both the electrode array and the probe electrode to be placed witha relatively steep angle of surgical approach through a shared incision.Such an approach can be achieved by performing a standard surgicallaminectomy or using a surgical tubular retractor system, such as theMetRX or the Swivel retractor, modified if required to provideappropriate guides and anchors to facilitate the placement of both theprobe electrode and the insertion tool for the SCS electrode.

In other embodiments, percutaneous implantation of a paddle lead may beperformed, as follows. A standard 14 gauge tuohy needle is used toaccess the epidural space. A guide wire is then inserted through theneedle to allow access to the epidural space. The standard needle isthen removed; a custom needle is then passed over the guide wire withthe tip just entering the epidural space. The tip has a sleeve toprevent coring of the tissue. The guide wire and sleeve are removedallowing the custom paddle lead to pass into the epidural space. As thefolded lead enters the epidural space it is separated to allow it tounfurl and lie flat over the dorsal columns. A stylet is used to helpposition the lead.

As shown in the cross sectional view of FIG. 5b , probe electrode 500comprises an electrode element 502 which extends widely in themediolateral direction relative to the spinal cord 180. Further, astimulus intensity delivered by the probe electrode element 502 is setto be significantly above a stimulus threshold. The stimulus thresholdfor the recording of ECAPs on the electrode array 150 can be identifiedin accordance with any suitable technique. Delivery of a sufficientlylarge stimulus from element 502 will create a region of recruitment 504which is sufficiently large to recruit action potentials within most ifnot all of the ascending fibres of the dorsal column 182. As can be seenthe wide extent of element 502 means that, even though the probeelectrode 500 and the associated region of recruitment 504 will notnecessarily be centrally positioned about the physiologic midline 184 ofthe spinal cord 180, most if not all of the ascending fibres of thedorsal column 182 will nevertheless be recruited. It is to beappreciated that any other configurations of the probe electrode whichachieve a corresponding effect are within the scope of the presentinvention.

Because probe electrode 500 has been inserted caudally of electrodearray 150 in the manner shown in FIG. 5a , the orthodromic rostralpropagation of the compound action potential evoked by a single stimulusdelivered by probe electrode 500 will take such an action potential pastelectrode array 150. Alternative embodiments may position the probeelectrode 500 rostrally of the electrode array 150, and exploitantidromic caudal propagation of the compound action potential along thedorsal column 182 from the probe electrode 500 to the electrode array150.

Once again, due to the difficulties of accurate implantation, electrodearray 150 will not necessarily be centrally positioned over thephysiologic midline 186 of the spinal cord 180. It is further noted thatthat midline 186 at the location of the array 150 may or may not alignprecisely with the midline 184 at the location of probe 500.

The compound action potential evoked by the probe electrode 500propagates rostrally within the dorsal column 182 and passes electrodearray 150, as shown in the cross sectional view of FIG. 5c , where it issimultaneously sensed by sense electrodes 156 and 158. Because most ifnot all of the ascending fibres of the dorsal column 182 have beenrecruited by probe electrode 500, the electric field of the compoundaction potential can be considered to be centrally located on thephysiologic midline 186. Consequently, a first field strength of thecompound action potential sensed by sense electrode 156 depends on thedistance of the sense electrode 156 from the midline 186, and a secondfield strength of the compound action potential sensed by senseelectrode 158 depends on the distance of the sense electrode 158 fromthe midline 186. The first field strength and second field strength maythen be compared to determine which sense electrode is closer to themidline 186, and an indication may be given to a surgeon as to whichdirection mediolaterally the array 150 should be moved in order toimprove the position of the array during surgery.

The above described actions can then be incorporated into animplantation process, as follows:

-   -   1. Surgical approach and placement of the probe electrode 500;    -   2. Insertion of the tip of the electrode array 150 and        connection of the array 150 to the recording system;    -   3. Stimulation amplitude adjustment of the probe electrode 500        by increasing the amplitude, until the threshold for ECAP        generation is reached, as measured by the electrodes on the        inserted tip of array 150. The amplitude is further increased to        be 1.5× or 2× the threshold current;    -   4. The electrode array 150 is then further inserted in the        epidural space by manipulation with forceps or other appropriate        surgical tool;    -   5. The amplitude of the ECAPS is continuously monitored and        displayed. The implanting surgeon manipulates the electrode to        achieve a balance of ECAP amplitudes from electrodes on opposing        lateral sides of the electrode array 150.    -   6. When the left and right most lateral electrodes 156 and 158        are producing the same amplitude ECAP responses, the electrode        array 150 is aligned with the electrophysiological midline.

FIGS. 5d and 5e illustrate experimental verification of the principlesof FIGS. 5a-5c . Data was obtained from a patient implanted with a StJude Penta™ lead 550 shown in FIG. 5d . FIG. 5e shows that the amplitudeof the ECAPs recorded on the electrodes in line with the stimulationwere larger compared to those on either side (more lateral), while FIG.5f shows that the latency of the N1 peaks remained the same. FIGS. 5d-5f further illustrate that the electrically evoked compound actionpotential can be used to locate the midline of the dorsal column with asingle electrode array that has a number of lateral contacts.Stimulating at the centre of the electrode and then measuring theamplitudes at each of the lateral contacts thus reveals theelectrophysiological midline. The midline is identified by comparing theamplitudes of the responses at the various contacts and identifying themaximum amplitude. This requires an electrode with a large number oflateral spaced contacts and a stimulating electrode that produces apredominantly midline response.

Notably, the method of FIG. 5 does not require patient feedback so thatthe patient can remain under general anaesthetic throughout. Moreover,this method avoids the need for more complex recording of somatosensorycortex potentials. Further, because the patient is under generalanaesthetic the possible recruitment of motor and/or pain fibres by thelarge stimulus delivered by probe electrode 500 will not cause patientdiscomfort.

FIGS. 6 to 11 illustrate the detection of lateral lead position byreference to the production of late responses, or motor activity, inaccordance with another embodiment of the present invention. A patienthad been previously approved for the implantation of a spinal cordstimulator to treat their pain. The patient was anaesthetised andprepared for paddle lead implantation. Once in place the lead wasconnected to a stimulating and recording system and ECAPs were monitoredduring surgery. The S4 Lamitrode electrode array 602 was insertedrostrally and was connected to channels 1 to 4 of the stimulating andrecording system, while the S8 Lamitrode electrode array 604 wasinserted caudally and connected to channels 9 to 16 of the stimulatingand recording system, in the manner shown in FIG. 6 a.

ECAPs were recorded on the S8 Lamitrode both during the procedure andwhile closing, with stimulation on either the S4 or S8 Lamitrode. FIG.6b shows ECAP signals recorded from the caudal end (i.e. from channels9-11) of the S8 Lamitrode 602, while stimulating at the rostral end(i.e. channels 14-16, in tripolar configuration).

FIG. 7a shows recordings obtained from electrodes 13-16 during theprocedure, while FIG. 7b is an enlarged view of the recordings of FIG.7a during the time period 0-5 ms. Notably, no late responses can be seenin the time period 5-25 ms in FIG. 7a . In FIG. 7b , small ECAP signalscan be seen propagating from CH16 to CH13.

FIG. 8a shows recordings on electrodes 13-16 during closing, while FIG.8b is an enlarged view of the recordings of FIG. 8a during the timeperiod 0-5 ms. Strong late responses are visible in FIG. 8a in the timeperiod 5-25 ms, which corresponded with observed patient twitching. InFIG. 8b , no ECAP signals can be seen propagating from Ch16-13.

Due to the strong twitching observed in the patient during closing, thecurrent was not increased beyond 2.2 mA, while it was previouslyincreased beyond that level during the procedure without issue. Duringthe procedure late responses were observed at 3.39 mA, although thesewere significantly smaller (<50%) than those observed during closing at2.2 mA (less than 60% of that current).

FIG. 9a shows the electrode configurations used to obtain the data ofFIGS. 9b, 9c, 10a and 10b . In particular, stimuli were delivered bychannels 1-3 on electrode array 602, while recordings were taken fromchannels 16-13 on electrode array 604.

FIG. 9b illustrates ECAP signals propagating down the S8 lead 604,during the procedure, at 3.39 mA of stimulation. FIG. 9c is an enlargedview of the recordings of FIG. 9b , during the period 0-5 ms.

FIG. 10a is a plot of signal strength obtained on Channel 16, during theprocedure, as the stimulus current was increased to 2.2 mA. FIG. 10b isa plot of signal strength obtained on Channel 16, during closing, as thestimulus current was increased to 2.2 mA. FIG. 10b shows the appearanceof the late response at approximately 1.7 mA during closing, between 5and 15 ms, which continues to increase with increasing current above 1.7mA. In contrast, no late response is observed during the procedure, i.e.in FIG. 10 a.

To explain the results of FIGS. 9 and 10, the electrophysiologicalposition was correlated with an anatomical post-operative CT image,shown in FIG. 11. The CT image confirmed that the S4 lead was lateral onthe left side, in particular being 15 mm left of midline at the top ofC6, and being 9 mm left of midline at the bottom of C7. The proximity tothe dorsal roots coincides with an early onset of the late response andlack of ECAP signals. Thus, stimulating on the S8 Lamitrode 604 showedno significant difference in ECAP amplitude for similar currentamplitudes, and no sign of a late response. Stimulating on the S4 leadshowed a decrease in the amplitude of the ECAP and a subsequent increasein the late response during closing. The appearance of late responsescoincided with an increase in muscle activity—observed as twitching inthe patient.

FIGS. 6 to 11 thus illustrate that monitoring the amplitude and latencyof the ECAP as well as late response during lead insertion is a useful,accessible tool to aid lead placement. The data shows that it ispossible to determine if the lead is lateral, near the dorsal roots andestimate its orientation with respect to the physiological midline ofthe spinal cord. Examining the presence of late responses can identifythe mediolateral location of the lead. Late responses are related to theactivation of roots and therefore if two leads are implanted and lateresponses are only seen on one side this would indicate that that leadis closer to the roots.

FIG. 12 illustrates another embodiment of the invention, in which thedorsal-ventral depth of the electrode, or its relative position from thesurface of the spinal cord, is determined. In this embodiment, the probeelectrode comprises two sets of stimulating contacts, each set being ata unique height above the dorsal column.

FIG. 12A illustrates how the amplitude of the observed ECAP response, asmeasured by the negative amplitude of the N1 peak, varies with thedistance of the axon from the recording electrode. As can be seen fromFIG. 12A, larger responses are observed if the fibres are closer to theelectrodes, and the amplitude of the observed response varies with thedistance r from the fibre by approximately 1/r². The present embodimentrecognises that a relative measure of the distance (x) of the electrode1256 from the spinal cord 1280 can be obtained in the following manner.Consider a probe electrode 1260 with a least two electrode contacts1262, 1264, which are separated by a vertical distance h above thespinal cord, as shown in FIG. 12b . The probe electrode heightseparation h can be precisely known. As discussed above in relation toFIG. 5, the electrode contacts 1262 and 1264 can each be made to extendmediolaterally from one side of the cord to other in such a manner as torecruit the maximal amount of fibres of the dorsal column of the cord1280.

The probe electrodes 1262, 1264 are preferably mounted on a surgicaltool and inserted in the retrograde manner in the epidural spaceopposite to the direction of the insertion of the SCS electrode 1256, inthe manner shown in FIG. 5a . The probe electrode is stimulated in analternate manner between the two electrode positions from the upperposition 1262 to the lower position 1264. The frequency of thestimulation will allow the convenient measurement of the ECAP responsesby the SCS electrode 1256 from both stimulating electrodes 1262, 1264.

The distance x between the SCS electrode 1256 and the spinal cord 1280can vary with insertion, or patient movement such as breathing. Theheight r of the stimulating electrode 1264 is unknown, but remains fixedwith respect to the spinal cord 1280 due to the temporary fixing of theprobe electrodes throughout the procedure. As illustrated in FIG. 12c ,the relative distance from the cord 1280 to the SCS electrode 1256 canbe determined by examining the difference in the observed ECAPamplitudes evoked by delivering the same intensity stimuli from therespective electrodes 1262, 1264.

Suitable adjustment of FIG. 12c may allow for the curve to be stepped toaccount for the transition of the propagating electric field fromtissue, to the dielectric substrate material bearing electrodes 1262,1264. Moreover, while electrode 1262 is sensing/stimulating, electrode1264 should be electrically floating to minimise shielding of theinteraction between electrode 1262 and the spinal cord 1280.

As shown in FIG. 12c , the amplitude difference a of the ECAP asmeasured by the N1 peak from the two different height probe electrodesis sensitive to the height of the electrode 1256 above the spinal cord1280. The closer the measurement electrode 1256 is to the cord 1280, thelarger the amplitude a of the differences, noting a₂>a₁ in FIG. 12 c.

The design of the probe electrode 1260 needs to be considered carefully.It is required to stimulate the same fibres of the spinal cord 1280,from two (or more) different heights. The stimulation location in thecaudal rostral direction for the two stimulating electrodes shouldideally be at the same caudal-rostral location or as close to each otheras possible so as the ECAP responses produced have the same distance topropagate to avoid the problem of different propagation distancesresulting in different amplitudes of response. An electrode contact 1260that achieves this arrangement is depicted in FIG. 13, in both elevationand plan view. It consists of interposed electrode contacts, whereby oneset 1262 of contacts is present on the surface and the other set 1264 isseparated by distance (h) at another plane in the electrode. The digitsare connected together and form a single large stimulating electrode ofa wide extent mediolaterally, and with two alternative heights above thedorsal column. Such embodiments thus recognise that not only is itimportant to be able to position the lead in the dorsolateral androstrocaudal direction to stimulate the appropriate dermatome, it alsoimportant to know where the lead is in the dorsal ventral direction. Thedistance from the spinal cord to the electrode in the dorsal ventraldirection affects both the power consumption and the degree to whichadjustments of the stimulation current can control the location andstrength of the paraesthesia or level of pain relief. For closed loopcontrol of SCS, the closer the lead is to the spinal cord the smallerthe current that is required to stimulate the target. In turn thiscorresponds to a larger amplitude of the actual compound actionpotential generated by a similar size current. Sense electrodes closerto the spinal cord will sense a stronger observed signal for a givenECAP, as compared to sense electrodes further away, improving signal tonoise quality in ECAP measurements. Increasing the amplitude of the ECAPis desirable to allow finer closed loop control. Positioning electrodescloser to the dura also results in lower currents required forstimulation and lower corresponding artifacts of stimulation in ECAPmeasurement.

FIG. 14a illustrates a further embodiment of the invention, in whichECAPs evoked directly on the spinal cord are combined with peripheralnerve stimulation, whereby the rostrocaudal location of the lead can beidentified. In this embodiment, it is desired to position a stimuluselectrode 1452 of an electrode array 1450 physiologically adjacent to aselected nerve root 1470 with an associated dermatome within whichparaesthesia is required. A TENS machine 1490 is used to stimulate theperipheral nerve(s) associated with nerve root 1470, thereby evokingcompound action potentials which propagate rostrally to the brain vianerve root 1470. TENS machine is operated at a fixed location and at afixed intensity so as to produce a train of substantially constantaction potentials. Simultaneously, the chosen stimulus electrode 1452directly stimulates the spinal cord 1480. Sense electrodes 1456 and 1458sense the resultant neural activity produced from 1490 and 1452, as itcontinues to propagate rostrally. The present embodiment recognises thatthe ECAPs evoked from stimulus electrode 1452 collide with, or interferewith, the compound action potentials evoked at the periphery by TENSdevice 1490, and further, that the maximal interference between the twotypes of ECAPs occurs when the location of electrode 1452 is optimalphysiologically relative to nerve root 1470. Accordingly, the method canbe performed while adjusting the caudorostral position of array 1450 toseek an array location at which maximal ECAP interference occurs. Inother embodiments the sense electrode(s) may be positioned on a separatesense electrode array and for example may be temporarily implanted onlyfor the duration of the implantation procedure.

FIG. 14b illustrates such ECAP interference or collision. FIG. 14b showsthe observed response 1402 from a single electrode in response to tibialnerve stimulation alone, the response 1404 from tibial nerve stimulationsimultaneously with spinal cord stimulation, and the response 1406observed when performing spinal cord stimulation only, withoutperipheral stimulation. The delay time to the dorsal column stimuliwhich produces the most attenuation allows estimation of the totallength of the fibre from the point where the stimulus is presented.

The ability to monitor, and control optimisation of, the mediolateral,caudorostral and/or dorsoventral location of the electrode, relative tophysiological characteristics of the dorsal columns rather thananatomical markers, will thus enable a much higher precision ofimplantation. The present invention may thus provide feedback to asurgeon that allows the lead to be steered to optimize the finalimplanted location of the spinal cord stimulation lead. To do sorequires surgical tools to assist in the steering and placement ofelectrodes. Some embodiments may therefore involve a lead comprising alongitudinal pocket or similar parts designed to receive an insertiontool.

In all described embodiments the determined position information can bepresented to the surgeon by any suitable means, such as by an acoustictone with pitch indicating relative height or position, or a visualindicia, or otherwise.

It will be appreciated by persons skilled in the art that numerousvariations and/or modifications may be made to the invention as shown inthe specific embodiments without departing from the spirit or scope ofthe invention as broadly described. The present embodiments are,therefore, to be considered in all respects as illustrative and notlimiting or restrictive.

1. A method of surgically positioning an electrode array at a desiredimplantation location relative to a nerve, the method comprising:implanting a temporary probe electrode adjacent to the nerve and at alocation which is caudorostrally separate to the desired implantationlocation of the electrode array; temporarily fixing the implantedposition of the probe electrode relative to the nerve; duringimplantation of the electrode array, applying electrical stimuli fromone of the temporarily fixed probe electrode and the electrode array, toevoke compound action potentials on the nerve; sensing, from at leastone electrode of the other of the temporarily fixed probe electrode andthe electrode array, the compound action potentials evoked by thestimuli; and determining from the sensed compound action potentials aposition of the electrode array relative to the nerve.
 2. The method ofclaim 1 wherein the probe electrode is surgically introduced via thesame incision as the electrode array.
 3. The method of claim 1 whereinthe desired positioning of the electrode array is relativemediolaterally to a physiologic midline of the nerve.
 4. The method ofclaim 3 wherein the probe electrode is configured to simultaneouslystimulate an even distribution of fibres mediolaterally across thenerve.
 5. The method of claim 3 wherein identification of thephysiologic midline of the nerve, and positioning of the electrode arrayrelative to the identified midline, is achieved by providing twolaterally spaced apart sense electrodes on the electrode array, andmonitoring a relative strength of the compound action potential sensedby each of the sense electrodes.
 6. The method of claim 1 wherein aradial spacing of the electrode array from the nerve is determined. 7.The method of claim 6 wherein the probe electrode comprises first andsecond stimulus electrodes each at distinct radii away from the nerve,used to deliver stimuli of equal intensity, at different times.
 8. Themethod of claim 1 wherein the probe electrode is fixed by beingtemporarily anchored upon a vertebra, within the epidural space.
 9. Themethod of claim 1 wherein the probe electrode is a peripheral nervestimulator delivering transcutaneous stimuli, to evoke CAPs onperipheral nerve(s) at a location of interest.
 10. The method of claim 9wherein an array location at which sense electrodes sense a maximalcollision of CAPs evoked by spinal cord stimulus electrodes with CAPsevoked by the peripheral nerve stimulator is taken to be an optimalcaudorostral position of the spinal stimulus electrodes relative to thelocation of interest.
 11. A system for positioning an electrode array ata desired implantation location relative to a nerve, the systemcomprising: a temporary probe electrode configured to be implantedadjacent to the nerve at a location which is caudorostrally separate tothe desired implantation location of the electrode array, and configuredto be temporarily fixed relative to the nerve while implanted; anelectrode array configured to be implanted adjacent to the nerve at thedesired implantation location, and comprising at least one electrodeconfigured to evoke or sense compound action potentials; and acontroller configured to: cause electrical stimuli to be applied fromone of the temporarily fixed probe electrode and the electrode array toevoke compound action potentials on the nerve during implantation of theelectrode array; sense from at least one electrode of the other of thetemporarily fixed probe electrode and the electrode array the compoundaction potentials evoked by the stimuli; and determine from the sensedcompound action potentials a position of the electrode array relative tothe nerve.
 12. A non-transitory computer readable medium for surgicallypositioning an electrode array at a desired implantation locationrelative to a nerve, comprising instructions which, when executed by oneor more processors, causes performance of the following: computerprogram code means for, during implantation of the electrode array,applying electrical stimuli from one of the electrode array and a probeelectrode which is temporarily fixed adjacent to the nerve at a locationwhich is caudorostrally separate to the desired implantation location ofthe electrode array, to evoke compound action potentials on the nerve;computer program code means for sensing, from at least one electrode ofthe other of the electrode array and the probe electrode, the compoundaction potentials evoked by the stimuli; and computer program code meansfor determining from the sensed compound action potentials a position ofthe electrode array relative to the nerve.